Loss of SMAD4 Expression Is a Poor Prognostic Factor in Ampullary Adenocarcinoma
Ahmad Alkhasawneh, Lizette Vila Duckworth, Neelam Desai, Xiaomin Lu, Alex Sommerfeld, Thomas George, Tania Zuluaga Toro. University of Florida, Gainesville, FL
Background: Adenocarcinomas of the ampulla of Vater may be classified based on morphology into biliary and intestinal subtypes, with the former having a more aggressive behavior. SMAD4 is a tumor suppressor gene that when down regulated has been shown to be an adverse prognostic factor in pancreatic adenocarcinoma. Though a prior study failed to demonstrate a difference in SMAD4 expression in intestinal versus biliary subtypes of ampullary adenocarcinomas (McCarthy et al. 2003), there is limited data on SMAD4 expression in ampullary tumors.
Design: 63 cases of ampullary adenocarcinomas resected between 2000 and 2011 were assessed for SMAD4 expression by immunohistochemistry. Morphologic type (intestinal versus biliary or indeterminate), age, gender, tumor stage, lymph node (LN) status, and measures of clinical outcome (death, recurrence) were recorded. SMAD4 expression was assessed as follows (adapted from Tascilar et al. 2001): negative (complete absence), trace (weak reactivity relative to surrounding normal pancreas), focal (two cell populations with a subset of clearly negative cells) and positive (strong staining comparable to surrounding pancreas).
Results: 22 cases were SMAD4 negative, 28 had decreased SMAD4 expression (9 focal, 19 trace), and 13 were SMAD4 positive. 68% (15/22) of the SMAD4 negative patients had biliary morphology, while 38% (5/13) of SMAD4 positive were of biliary subtype. Tumor stage was higher in SMAD4 negative patients (72% were stage T3/T4) versus SMAD4 positive patients (54% were T3/T4). Lymph node metastasis was also higher among the SMAD4 negative patients (50% LN positive) versus SMAD4 positive patients (38%). In patients with available clinical follow-up, 57% (8/14) of patients who recurred were SMAD4 negative. Death rate was also higher in SMAD4 negative patients (54%) versus SMAD4 positive patients (31%).
|SMAD4||Stage T1/T2||Stage T3/T4||Lymph node metastasis||Recurrence||Deceased|